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KMID : 0855520110240030165
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Korean Journal of Physical Anthropology
2011 Volume.24 No. 3 p.165 ~ p.174
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Inhibitory Effects of 1’,2’-Dihydrorotenone on Osteoclast Differentiation and Bone Resorption In Vitro and In Vivo
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Kim Kwang-Jin
Kwak Han-Bok
Choi Eun-Young
Oh Jae-Min
Choi Min-Kyu
Lee Jeong-Hugh
Song Mi-Jin
Ahn Yong-Hwan
Lee Myeung-Su
Lee Chang-Hoon
Park Seong-Hoon
Chae Soo-Uk
Kim Myung-Hee
Kim Seong-Hwan
Park Kie-In
Kim Kwang-Mee
Kim Ha-Young
Moon Seo-Young
Kim Jeong-Joong
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Abstract
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It is important to identify therapeutic compounds with no adverse effects for use in the chemotherapy of patients with bone-related diseases. The aim of this study was to identify a new compound that inhibits osteoclast differentiation and bone resorption. Herein, we examined the effects of 1’,2’-dihydrorotenone on osteoclast differentiation and bone resorption in vitro and in vivo. 1’,2’-dihydrorotenone inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation of cultured bone marrow macrophages (BMMs) in a dosedependent manner. However, 1’,2’-dihydrorotenone did not exert cytotoxic effect on BMMs. 1’,2’-dihydrorotenone suppressed the expression of c-fos and NFATc1 as well as osteoclast-specific genes in BMMs treated with RANKL. Treatment with RANKL inhibited the expression of inhibitors of differentiation/DNA binding (Id)1, 2, and 3; however, in the presence of 1’,2’-dihydrorotenone, RANKL did not suppress the expression of Id1, 2, and 3. Furthermore, 1’,2’-dihydrorotenone inhibited bone resorption and considerably attenuated the erosion of trabecular bone induced by lipopolysaccharide treatment. Taken together, these results suggest that 1’,2’-dihydrorotenone has the potential to be applied in therapies for bone-related diseases.
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KEYWORD
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Osteoclast, RANKL, 1’, 2’-dihydrorotenone, Resorption
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